THE EFFECTS OF ALTITUDE TRAINING ON BLOOD GENE EXPRESSION PROFILES IN ORDER TO COMPARE AND DIFFERENTIATE FROM A PREVIOUSLY IDENTIFIED “MOLECULAR SIGNATURE” OF RHUEPO DOPING

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Abstract

Aims

Current testing methods for the abuse of recombinant human erythropoietin for performance enhancement are inadequate. Recently ‘omics’ technologies have been used, successfully, to demonstrate a ‘molecular signature’ of rHuEPO administration. The same technologies can be applied in altitude-trained individuals in an attempt to differentiate rHuEPO administration and altitude training at a gene expression level. This approach has the potential to improve current doping detection methods, such as the Athlete Biological Passport (ABP). The aim of this project was to assess the effects of altitude training on blood gene expression profiles in order to compare and differentiate from a previously identified “molecular signature” of rHuEpo doping.

Methods

20 endurance trained individuals participated in the study. 12 individuals (5 Female, 7 Male) trained at ∼2320 m altitude (Sierra Nevada, Spain) for 17 days and 8 individuals (3 Female, 5 Male) trained at sea-level (London, England). Blood samples were taken for haematological and gene expression analysis at baseline, during, and post-48hr, 1 week, 2 weeks and 4 weeks-post altitude exposure. Gene expression was analysed using Affymetrix QuantiGene Plex Assay, focussing on a subset of 50 target genes.

Results

28 of the target genes were identified as significant by the overall F-test (FDR adjusted P value <0.05). Two trends towards significantly differential expression were identified. 20 genes were found to be trending towards under expression 1-week after altitude exposure (FDR>0.06). 13 genes were found to be trending towards over expression during altitude exposure (FDR>0.07). There were no significant changes in the measured haematological parameters.

Conclusions

This study gives an insight into the gene expression signature of altitude exposure in endurance-trained athletes. Altitude exposure cannot currently be confidently differentiated from rHuEPO doping, using gene expression profiles alone. These findings add to the evidence supporting the use of “Omics” technologies, alongside current anti-doping strategies.

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